The immune system defends the human body against pathogen infection, cellular transformation, and physical/chemical damage. Its dysfunction, either overactive or underactive, leads to various disorders. The dysfunction can be caused by aging, development defects, diseases, and medical treatment (e.g., chemotherapy or immuno-suppression). There is a need for drugs and reagents for treatment of immune disorders. The present invention addresses and meets the need by identifying DC-SIGN binding peptides that can modulate immune responses.
DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a C-type lectin receptor present on various immune cells, including macrophages and dendritic cells. DC-SIGN recognizes high-mannose glycans from a variety of pathogens, and acts as a pattern recognition receptor bridging innate and adaptive immunity (Geijtenbeek et al. Nat Rev Immunol 9, 465-479 (2009)). Ligation of DC-SIGN by bacteria-derived mannosylated glycans can induce their internalization, and also synergize with other innate receptor pathways promoting inflammation and resistance to infection. The immuno-suppressive potential of DC-SIGN has been documented following ligation by HIV8-derived gp120 or α-DC-SIGN antibody, which promotes the development of tolerogenic, IL-10 producing, dendritic cells, and interferes with TLR signaling (Gringhuis et al. Immunity 26, 605-24 616 (2007) and Hodges et al. Nat Immunol 27 8, 569-577 (2007)). Also, binding of IgG Fcs with glycans terminating in α2,6 sialic acids (sFc) to DC-SIGN results in an anti-inflammatory response (Kaneko et al. Science 313, 670-673 (2006) and Anthony et al. Proc Natl Acad Sci USA 13 105, 19571-19578 (2008)).